The goal of this project is to isolate, sequence, and characterize the genes expressed in human brain. As many as half of the more than 50,000 human genes are believed to be expressed in the brain. While sequencing the human genome is expected to take over 15-20 years, sequencing a large number of cDNA clones can readily provide coding sequence data on genes expressed in tissues. We are building a large library of clones and sequences of human brain cDNA clones. One thousand human brain sequences have been completed in the first 3-4 months of this project. Over half of the genes isolated are totally new genes, not previously identified or cloned. An additional percentage are new human genes, having been previously isolated from other species. Computer analysis of the protein sequences at the primary and secondary structural level is assisting clone identification. DNA and predicted protein sequences will be examined for the presence of conserved primary structure motifs and relationships to previously sequenced genes. Further characterization of potentially interesting clones will include chromosome localization, examination of tissue distribution of expression, and evolutionary conservation. The availability of a broad-based library of cDNA sequences will also facilitate identification of coding regions in genomic sequences as well as provide a starting point for individual cloning projects. A variety of approaches are being used to select brain-specific clones and to eliminate highly represented sequences.